Numerical analysis of urine flow through the side holes of a double J stent in a ureteral stenosis.
Ureteral stenosis presents with a narrowing in the ureter, due to an intrinsic or extrinsic ureteral disease, such as ureter cancer or retroperitoneal fibrosis. The placement of a double J stent in the upper urinary system is one of the most common treatments of ureteral stenosis, along with the insertion of a percutaneous nephrostomy tube into the renal pelvis. The effect that the side holes in a double J stent have on urine flow has been evaluated in a few studies using straight ureter models. In this study, urine flow through a double J stent's side holes was analyzed in curved ureter models, which were based on human anatomy. In ureteral stenosis, especially in severe ureteral stenosis, a stent with side holes had a positive effect on the luminal and total flow rates, compared with the rates for a stent without side holes. The more side holes a stent has, the greater the luminal and total flow rates. However, the angular positions of the side holes did not affect flow rate. In conclusion, the side holes in a double J stent had a positive effect on ureteral stenosis, and the effect became greater as the ureteral stenosis became more severe.


The frequency and distribution of intratubular trophoblast in association with germ cell tumors of the testis.
Although the presence of intratubular trophoblast (ITT) has been reported, its frequency and distribution in association with germ cell tumors (GCT) have not been investigated. Beta human chorionic gonadotropin (hCG) is a sensitive immunohistochemical marker of syncytiotrophoblast. We therefore wished to investigate whether intratubular trophoblastic elements could be identified adjacent to invasive tumors using immunohistochemistry against hCG. Seventy-five GCTs were examined. Immunochemistry was performed for hCG. Both invasive tumor and seminiferous tubules were examined for positive staining. The seminomas showed ITT in five of 29 cases. All these cases had trophoblastic cells as part of the invasive tumor. Only one of 36 cases of nonseminoma and one of nine of the mixed GCTs (11%) showed ITT. Again, all of the positive cases had hCG-positive trophoblastic cells within the invasive tumor. ITT can be identified adjacent to GCTs in a significant number of cases. We suggest that this is a genuine in situ lesion, associated with seminomas with syncytiotrophoblastic cells. Differentiation toward trophoblastic elements in GCTs may occur at an earlier stage of their pathogenesis than has been previously recognized.


Active immunization for prevention of De novo hepatitis B virus infection after adult living donor liver transplantation with a hepatitis B core antigen-positive graft.
De novo hepatitis B virus (DNHB) infections may occur in recipients who do not receive prophylaxis after liver transplantation (LT) with antibody to hepatitis B core antigen (anti-HBc)-positive donor grafts. Active immunization has been shown to prevent DNHB in pediatric recipients. Our aim is to investigate the efficacy of HBV vaccination for preventing DNHB in adult living donor liver transplantation (LDLT). In total, 71 adult antibody to hepatitis B surface antigen (anti-HBs)-negative LDLT patients who received anti-HBc+ grafts from 2000 to 2010 were enrolled into this study. Patients were given hepatitis B virus vaccinations with the aim of achieving anti-HBs > 1000 IU/L before transplant and >100 IU/L after transplant. The cohort was stratified into 3 groups: patients with pretransplant anti-HBs titer of > 1000 IU/L without the need for posttransplant prophylaxis (group 1, n = 24), patients with pretransplant low titer of <1000 IU/L who were given posttransplant lamivudine prophylaxis and responded appropriately to posttransplant vaccination by maintaining anti-HBs titers of > 100 IU/L (group 2, n = 30), and low titer nonresponders (anti-HBs titer of < 100 IU/L despite vaccination), for whom lamivudine was continued indefinitely (group 3, n = 17). All DNHB occurred in group 3 patients with posttransplant anti-HBs levels of < 100 IU/L, with an incidence rate of 17.6% compared with 0% in patients with posttransplant anti-HBs levels of > 100 IU/L (P = 0.001). A pretransplant anti-HBs level of >1000 IU/L was significantly associated with early attainment and a sustained level of posttransplant anti-HBs of >100 IU/L (P < 0.001). Active immunization is effective in preventing DNHB in adult LDLT if the posttransplant anti-HBs level is maintained above 100 IU/L with vaccination. Antiviral prophylaxis can be safely discontinued in patients who obtain this immunity. Liver Transplantation 23 1266-1272 2017 AASLD.


Socio-economic position over the life course and all-cause, and circulatory diseases mortality at age 50-87 years: results from a Swedish birth cohort.
Both child and adult socio-economic position (SEP) predict adult mortality, but little is known about the variation in the impact of SEP across the life course. The Uppsala Birth Cohort Study is a representative birth cohort born 1915-1929 in Uppsala, Sweden. For the 5,138 males and 5,069 females alive in 1980, SEP was available at birth; in adulthood (age 31-45); and in later life (age 51-65). Follow-up for mortality (all-cause, and circulatory disease) was from 1980 to 2002. To test which life course model best described the association between SEP and mortality, we compared the fit of a series of nested Cox proportional hazards regression models (representing either the critical, accumulation or sensitive period models) with a fully saturated model. For all-cause mortality in both genders, the sensitive period model best described the influence of SEP across the life course with a heightened effect in later adult life (males: Hazard Ratio (95 % CI) for advantaged SEP: 0.89 (0.81-0.97) at birth, 0.90 (0.81-0.98) in adulthood, 0.74 (0.67-0.82) in later life; females: 0.87 (0.78-0.98), 0.95 (0.86-1.06), 0.73 (0.64-0.83)). The effect of SEP on circulatory diseases mortality in males was cumulative (HR: 0.84 (0.80-0.87) per unit time in advantaged SEP). For circulatory disease mortality among females, a sensitive period model was selected due to SEP in later adult life (HR: 0.64 (0.52-0.80)). These findings suggest that reducing inequality throughout the life course might reduce all-cause and circulatory disease mortality.


A preliminary study of the moderating role of church-based social support in the relationship between racist experiences and general anxiety symptoms.
The current study explores the potential buffering effect of church-based social support on the effect of racism on anxiety symptomology in a Black sample. Fifty participants completed a questionnaire packet containing measures of anxious arousal and stress (general anxiety) symptoms, church-based social support, and experience of racist events. Results indicated that church-based social support moderated the relationship between racist experiences and general anxiety symptoms such that at low levels of church-based social support the experiences of racism and stress (general anxiety) symptoms were significantly positively associated. The clinical implications of these findings and future research directions are discussed.


Intraperitoneal immunization with Urease loaded N-trimethyl Chitosan nanoparticles elicits high protection against Brucella melitensis and Brucella abortus infections.
Brucella (B) species are brucellosis causative agents, a worldwide zoonotic illness causing Malta fever in humans and abortion in domestic animals. In this work, we evaluated the vaccine potential of Trimethyl chitosan (TMC) nanoparticles formulation of Urease (TMC/Urease) against brucellosis. TMC/Urease nanoparticles and urease without any adjuvant were separately administered both orally and intraperitoneally. Intraperitoneal (i.p.) administration of urease alone as well as oral administration of both TMC/Urease nanoparticles and urease alone, elicited low titers of specific immunoglobulin G (IgG), while i.p. immunization with TMC/Urease nanoparticles induced high specific IgG production levels. As it was indicated by the cytokine assay and the antibody isotypes, i.p. immunization by urease alone, and TMC/Urease nanoparticles induced a mixed Th1-Th2 immune response, whereas oral administration of both urease alone and TMC/Urease nanoparticles induced a mixed Th1-Th17 immune response. In lymphocyte proliferation assay, spleen cells from i.p.-vaccinated mice with TMC/Urease nanoparticles showed a strong recall proliferative response. Vaccinated animals were challenged with virulent strains of B. melitensis and B. abortus. I.p. vaccination with TMC/Urease nanoparticles resulted in a high degree of protection. Altogether, our results indicated that TMC nanoparticles are a potent delivery system for i.p.-administered Brucella antigens.


Assessment of Ethnicity in Indian Population using Tooth Crown Metric Dental Traits.
Tooth crown dimensions vary between different ethnic groups, providing insights into the factors controlling human dental development. This present study compares permanent mesiodistal (MD) and buccolingual crown dimensions between four ethnic groups, highlighting patterns of tooth size between these groups and considers the findings in relation to genetic and environmental influences. MD and buccolingual tooth crown dimensions were recorded using digital vernier calipers on dental casts derived from four different human population: Iranians, Hindus, Muslims, and Christians. Obtained measurements were subjected to statistical analysis. The Christian sample was found to have the largest teeth overall, whereas the Iranian sample generally displayed the smallest MD and buccolingual crown dimensions (P < 0.001). Comparisons of coefficients of variation for teeth within each class showed that the later-forming teeth displayed greater variation in MD size than the earlier-forming teeth. The different patterns of tooth size observed between the study samples are thought to reflect differences in the relative contributions of genetic and environmental influences to dental development between the four population. Using a standardized methodology, significant differences in MD and buccolingual crown dimensions have been demonstrated between four human ethnic groups. There were also distinct differences in the patterns of crown size between the groups, with the later-forming teeth in each type generally showing greater size variation.


Relationships of pulmonary oxygen uptake kinetics with skeletal muscle fatigue resistance and peak oxygen uptake in healthy young adults.
[Purpose] The objective of this study was to determine the validity of pulmonary oxygen uptake kinetics in assessment of the ability of skeletal muscles to utilize oxygen. [Subjects] We evaluated 12 young, healthy males. [Methods] The subjects completed a series of tests to determine their peak oxygen uptake, pulmonary oxygen uptake kinetics at the onset of moderate-intensity treadmill exercise, and the rate of decline in electromyographic (EMG) mean power frequency (MPF) (EMG MPFrate) during one continuous, fatiguing, isometric muscle action of the plantar flexors until exhaustion at approximately 60% maximum voluntary contraction. We discussed the relationships between pulmonary oxygen uptake kinetics and EMG MPFrate reflecting the ability of skeletal muscles to utilize oxygen and between pulmonary oxygen uptake kinetics and peak oxygen uptake reflecting the ability to deliver oxygen to skeletal muscles. We hypothesized that pulmonary oxygen uptake kinetics may be more highly correlated with EMG MPFrate than peak oxygen uptake. [Results] Pulmonary oxygen uptake kinetics (33.9 ± 5.9 s) were more significantly correlated with peak oxygen uptake (50.6 ± 5.5 mL/kg/min) than EMG MPFrate (-14.7 ± 8.7%/s). [Conclusion] Pulmonary oxygen uptake kinetics is a noninvasive index that is mainly usable for evaluation of the ability of cardiovascular system to deliver oxygen to skeletal muscles in healthy young adults with slower pulmonary oxygen uptake kinetics (>20 s).


Carnitine palmitoyltransferase 1 (CPT1) alleviates oxidative stress and apoptosis of hippocampal neuron in response to beta-Amyloid peptide fragment Aβ25-35.
CPT1C, which is expressed in hippocampus, influences ceramide level, endogenous cannabinoid and oxidation process, as well as plays an important role in various brain functions such as learning. This study aimed to investigate the role of CPT1C in Alzheimer's disease (AD) and its underlying mechanism. We established a model of Alzheimer's disease in vitro by exposing primary hippocampal neurons to beta-Amyloid peptide fragment 25-35 (Aβ25-35). The cell viability, lactate dehydrogenase (LDH) level, expressions of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected using Cell Counting Kit-8 (CCK-8), LDH assay, ROS kits, malondialdehyde (MDA) kits and SOD kits, respectively. Moreover, the expression of oxidative stress-related proteins as well as the expressions of amyloid precursor protein (App), p-Tau andβ-site APP-cleaving enzyme1 (Bace-1) were measured using quantitative reverse transcription PCR (RT-qPCR) and western blot. Tunel and western blot were adopted to detect apoptosis as well as its related proteins. After the treatment of peroxisome proliferators-activated receptor alpha (PPARα), CPT1C expression was detected with the application of RT-qPCR and western blot. CPT1C expression was reduced in Aβ25-35-induced HT22 cells. Overexpression of CPT1C relieved cell viability and toxic injury as well as attenuated oxidative stress, apoptosis and expression levels of AD marker proteins. Moreover, higher doses of PPARα agonist activate the expression of CPT1C in Aβ25-35-induced HT22 cells. In conclusion, CPT1C alleviates Aβ25-35-induced oxidative stress, apoptosis and deposition of AD marker proteins in hippocampal neurons, suggesting that CPT1C has favorable effects on alleviating AD and participates in PPARα activation.


Effects of environmental pollutants on signaling pathways in rat pituitary GH3 adenoma cells.
An increased rate of acromegaly was reported in industrialized areas, suggesting an involvement of environmental pollutants in the pathogenesis and behavior of GH-secreting pituitary adenomas. Based on these premises, the aim of the study was to evaluate the effects of some widely diffused pollutants (i.e. benzene, BZ; bis(2-ethylhexyl) phthalate, DEHP and polychlorinated biphenyls, PCB) on growth hormone secretion, the somatostatin and estrogenic pathways, viability and proliferation of rat GH-producing pituitary adenoma (GH3) cells. All the pollutants induced a statistically significant increase in GH secretion and interfered with cell signaling. They all modulated the expression of SSTR2 and ZAC1, involved in the somatostatin signaling, and the expression of the transcription factor FOXA1, involved in the estrogen receptor signaling. Moreover, all the pollutants increased the expression of the CYP1A1, suggesting AHR pathway activation. None of the pollutants impacted on cell proliferation or viability. Present data demonstrate that exposure to different pollutants, used at in vivo relevant concentrations, plays an important role in the behavior of GH3 pituitary adenoma cells, by increasing GH secretion and modulating several cellular signaling pathways. These observations support a possible influence of different pollutants in vivo on the GH-adenoma aggressiveness and biological behavior.


Omission of Hemostatic Agents During Robotic Partial Nephrectomy Does Not Increase Postoperative Bleeding Risk.
The use of hemostatic agents (HA) during robotic partial nephrectomy (RPN) is largely empiric. We sought to assess the impact of HA on postoperative bleeding after RPN in a contemporary cohort. Using our institutional RPN database, we identified consecutive patients treated between 2010 and 2015. HA were routinely placed in the nephrectomy bed at the time of renorrhaphy until 2014 when their use was phased out to reduce cost. We compared postoperative bleeding outcomes (blood transfusion and hemoglobin decline) between patients who did and did not receive HA, after excluding patients with preoperative anemia (hemoglobin <11 g/dL) or high estimated blood loss (≥175 mL). The total inflation-adjusted costs (for 2015) of HA were calculated. Of 544 cases, HA were used in 240 (44.1%). The mean number of agents per case was 1.4 ± 0.73, including 77 (14.2%), 52 (9.6%), and 39 (7.2%) cases in which cellulose, fibrin, or gelatin-based agents were used alone, respectively, and 72 (13.2%) cases in which multiple agents were used. The mean cost of HA per case was $488 ± 421. Nearly 90% of cases were performed by surgeons who were beyond their learning curves. Overall, 13 (2.4%) patients were transfused, and the median hemoglobin decline was 2.2 g/dL (IQR, 1.4-3.0 g/dL). On univariate analysis, HA use and type of HA were not significantly associated with blood transfusion (p = 0.20 and p = 0.29, respectively), but were associated with hemoglobin decline (p = 0.01 and p = 0.02, respectively). After adjusting for covariates, HA use was no longer significantly associated with postoperative hemoglobin decline. In nonanemic patients with minimal intraoperative bleeding, HA use does not alter postoperative bleeding outcomes after RPN, suggesting that their routine use in this setting merits reconsideration. Further research is needed to determine if HA may be useful in certain high-risk situations.


Quantitative detection of hepatitis C virus (HCV) RNA in saliva and gingival crevicular fluid of HCV-infected patients.
The search for hepatitis C virus (HCV) in body fluids other than blood is important when assessing possible nonparenteral routes of viral transmission. However, the role of oral fluids in HCV transmission remains controversial. Here we quantitatively determined HCV RNA in saliva and gingival crevicular fluid (GCF) of anti-HCV-positive patients. Most patients (14 of 18; 78%) whose saliva specimens were negative had HCV RNA in their GCF. Most patients (20 of 26; 77%) had higher HCV RNA levels in their GCF than in their saliva. Although there was not a statistically significant correlation between the serum viral load and HCV level in saliva or GCF, patients with low serum HCV loads were less likely to have detectable HCV in their saliva. These findings have important implications for medical personnel and suggest that epidemiological studies designed to understand the significance of the oral route of transmission of HCV are warranted.


Medial restraints to anterior-posterior motion of the knee.
We investigated the motion of cadaver knees before and after section of the medial structures and anterior cruciate ligament. The knees were tested using a 5-degrees-of-freedom in vitro knee-testing apparatus that measured anterior-posterior, medial-hateral, and axial displacement as well as internal-external and valgus-varus rotation. The fiexion angle could be varied but was fixed for each individual test. A 125-newton anterior-posterior force was applied perpendicular to the tibial shaft and the resulting motion of the knee was measured. In five knees the anterior cruciate ligament was cut first, followed by progressive cuts of the structures on the medial side (superficial medial collateral ligament, deep medial ligament, oblique fibers of the superficial medial ligament, and the posteromedial part of the capsule). Conversely, in five knees the medial structures were progressively cut first, followed by section of the anterior cruciate ligament. Tests were performed after each cut. With an intact anterior cruciate ligament, progressive cutting of the medial side had no effect on anterior and posterior displacements. When section of the medial structures followed cutting of the anterior cruciate ligament, anterior displacement exceeded that seen after isolated section of the anterior cruciate ligament. The anterior and posterior load-tests were repeated with the tibia fixed in 5 degrees of internal and 5 degrees of external rotation. Fixed external notation had no effect on anterior and posterior displacements. Fixed internal rotation significantly decreased anterior displacement only when both the anterior cruciate ligament and the medial structures were cut. The amounts of tibial rotation and tibial torque resulting from the applied anterior and posterior forces were low compared with our previous results, and we attributed this to decreased constraints on motion of the knee in the current testing apparatus. Athletic injuries of the knee frequently involve both the anterior cruciate ligament and the medial side of the knee. Clinical studies have demonstrated that combined injuries of the anterior cruciate and medial collateral ligaments often cannot be successfully managed conservatively. Our in vitro findings support the clinical data and suggest that injuries to the medial structures further compromise anterior stability when they accompany anterior cruciate injuries.


Isolated Pulmonary Valve Endocarditis Complicated With Septic Emboli to the Lung Causing Pneumothorax, Pneumonia, and Sepsis in an Intravenous Drug Abuser.
Intravenous drug users are at increased risk for developing right-sided infective endocarditis involving the tricuspid and pulmonary valves. Isolated pulmonary valve endocarditis in intravenous drug users is very rare, and these patients often have more complications, such as pulmonary embolism, sepsis, and pneumonia. We report a case with pulmonary valve endocarditis and extensive pulmonary complications, including sepsis, septic emboli, pneumonia, and pneumothorax. Early identification of pulmonic valve endocarditis and treatment with appropriate antibiotics with or without surgical management should provide better outcomes, and clinicians need to think about pulmonary valve endocarditis in patients with complex respiratory presentations.


Two clerodane diterpenes isolated from Polyalthia longifolia leaves: comparative structural features, anti-histaminic and anti-Helicobacter pylori activities.
Phytochemical studies of methylene chloride soluble fraction from the 70% aqueous-alcoholic extract of Polyalthia longifolia (leaves) resulted in the isolation of two known clerodane diterpenes, namely: 16α-hydroxycleroda-3,13(14)-dien-16,15-olide (1) and (4→2)-abeo-16-hydroxy-cleroda-2,13(14)-dien-15,16-olide-3-al (2). The isolated compounds were evaluated for their anti-histaminic and anti-Helicobacter pylori activities. Compound 1 was more potent than 2 with IC50 29.7 μg/mL and 189.2 μg/mL in the anti-histaminic assay and MIC equals to 31.25 μg/mL and 125 μg/mL in the anti-H. pylori assay, as compared with diclofenac (IC50 = 17.9 μg/mL) and clarithromycin (MIC = 1.95 μg/mL), respectively. The differences in their structures, as well as their activity results, indicated important characteristic features necessary for activity. It was suggested that the decalin moiety in 1 was important for both activities. On the other hand, the (4→2)-abeo migration in 2 reduced both activities. The potent activities of 1 suggest its potential application as an anti-histaminic and antimicrobial agent.


Keeping abreast with long non-coding RNAs in mammary gland development and breast cancer.
The majority of the human genome is transcribed, even though only 2% of transcripts encode proteins. Non-coding transcripts were originally dismissed as evolutionary junk or transcriptional noise, but with the development of whole genome technologies, these non-coding RNAs (ncRNAs) are emerging as molecules with vital roles in regulating gene expression. While shorter ncRNAs have been extensively studied, the functional roles of long ncRNAs (lncRNAs) are still being elucidated. Studies over the last decade show that lncRNAs are emerging as new players in a number of diseases including cancer. Potential roles in both oncogenic and tumor suppressive pathways in cancer have been elucidated, but the biological functions of the majority of lncRNAs remain to be identified. Accumulated data are identifying the molecular mechanisms by which lncRNA mediates both structural and functional roles. LncRNA can regulate gene expression at both transcriptional and post-transcriptional levels, including splicing and regulating mRNA processing, transport, and translation. Much current research is aimed at elucidating the function of lncRNAs in breast cancer and mammary gland development, and at identifying the cellular processes influenced by lncRNAs. In this paper we review current knowledge of lncRNAs contributing to these processes and present lncRNA as a new paradigm in breast cancer development.


Risk of cardiovascular events and pulmonary hypertension following splenectomy - a Danish population-based cohort study from 1996-2012.
Splenectomized patients are at increased risk of cardiovascular events, but it remains unclear whether this is due to lack of the spleen or due to the underlying disease leading to splenectomy. We aimed to assess the risk of myocardial infarction, pulmonary hypertension, and stroke following splenectomy. We identified patients splenectomized in Denmark between 1996 and 2012. We constructed two comparison cohorts: an age- and sex-matched general population cohort and a disease-matched cohort based on the splenectomy-related underlying disease. We computed 5-year cumulative incidences and adjusted hazard ratios of myocardial infarction, pulmonary hypertension, and stroke for the three cohorts. The study included 5,306 splenectomized patients, 53,060 members of the general population, and 11,651 disease-matched patients. During the 5-year follow-up, 1.3% of splenectomized patients had a myocardial infarction versus 1.8% of the population cohort. The adjusted hazard ratio for myocardial infarction in splenectomized patients versus the population cohort was 1.24 (95% confidence interval: 1.01-1.52). The 5-year cumulative incidence of pulmonary hypertension was 0.4% among splenectomized subjects and 0.2% in the population cohort [adjusted hazard ratio 3.25 (95% confidence interval: 1.93-5.45)], while that of stroke was 3.3% among splenectomized patients versus 2.6% in the population cohort [adjusted hazard ratio 2.04 (95% confidence interval: 1.78-2.35)]. When comparing splenectomized subjects with the disease-matched cohort, only stroke risk was elevated, with 5-year risks of 3.0% and 2.3%, respectively [adjusted hazard ratio 1.56 (95% confidence interval: 1.26-1.92)]. In conclusion, splenectomized patients were at increased risk of stroke. Additionally, we found that underlying splenectomy-related diseases explained the increased risk of myocardial infarction and pulmonary hypertension following splenectomy.


Synthesis of phthalazinones via palladium(II)-catalysed intramolecular oxidative C-H/C-H cross-coupling of N'-methylenebenzohydrazides.
A palladium(II)-catalysed intramolecular oxidative C-H/C-H cross-coupling of N'-methylenebenzohydrazides to phthalazin-1(2H)-ones has been developed. This cyclization is believed to mechanistically proceed via electrophilic ortho-palladation and subsequent C-arylation of the carbon-nitrogen double bond.


Septic shock of early or late onset: does it matter?
To determine possible differences in morbidity and mortality between early and late onset of septic shock in ICU patients. Systematic data collection. Thirty-one-bed, mixed, medicosurgical ICU in a university hospital. All 65 patients who acquired septic shock after admission to the ICU between February 1999 and April 2000. None. Forty-one of the 65 patients presented with septic shock within 24 h of admission to the ICU (early septic shock [ESS]); the other 21 patients acquired septic shock > 24 h after ICU admission (late septic shock [LSS]). Eleven patients had a second episode (7 patients in the ESS group, and 4 patients in the LSS group), and 1 patient in the LSS group had a third episode of septic shock. Patients with ESS had higher APACHE (acute physiology and chronic health evaluation) II (mean +/- SD, 26 +/- 6 vs 20 +/- 6; p = 0.002) and sequential organ failure assessment (SOFA) scores (11 +/- 3 vs 7 +/- 3, p < 0.001) on ICU admission, and a higher blood lactate concentration at the onset of shock (median 3.70 mEq/L; interquartile range, 2.6 to 6.6 mEq/L; vs median, 2.50 mEq/L [interquartile range, 1.8 to 4.0 mEq/L], p = 0.03) than patients with LSS. However, the duration of septic shock (median, 42 h [interquartile range, 21 to 97 h] vs median, 93 h [interquartile range, 32 to 241 h], p = 0.058) and the length of ICU stay after the onset of septic shock (median, 75 h; [interquartile range, 38 to 203 h] vs median, 321 h [interquartile range, 96 to 438 h], p = 0.018), was shorter in patients with ESS than patients with LSS. The ICU mortality rate was 63% (26 patients) in the ESS group, and 88% (21 patients) in the LSS group (p = 0.071). At the onset of the first episode of shock, patients with ESS had higher SOFA scores (11 +/- 3 vs 9 +/- 3, p = 0.045), lower pH (7.24 +/- 0.15 vs 7.33 +/- 0.12, p = 0.01), and were treated with higher doses of dopamine (median, 20 microg/kg/min [interquartile range, 14 to 20 microg/kg/min] vs median, 12 microg/kg/min [interquartile range, 8 to 20 microg/kg/min], p = 0.028) than patients with LSS. Septic shock is more severe when of early onset, as reflected by more severe organ dysfunction, greater lactic acidosis, and higher vasopressor requirements, yet the outcome is better, as reflected by a shorter duration of the shock episode, shorter ICU stay, and slightly lower mortality rates. These differences may influence clinical trials of therapeutic agents for sepsis, and should be taken into account when analyzing the results.


Work-Related Intervention Needs and Potential Occupational Outcomes among Medical Assistants: A Cross-Sectional Study.
Medical assistants' (MAs) working conditions have been characterized as precarious, and workplace-related intervention needs have been identified. However, strategies to change the MAs adverse working conditions are mostly seen on an individual level, including leaving the employer or even the profession. Since such intentions are antecedents of actual turnover, we aimed to quantify the potential link of reported unmet intervention needs with unfavorable occupational outcomes. Data were collected by means of a nationwide survey among medical assistants (n = 994) in Germany (September 2016-April 2017). The three subscales working conditions, reward from the supervisor, and task-related independence were derived from a 12-item instrument regarding work-related interventions needs (the independent variables). We used subscale-specific z-scores and a total needs z-score. The four outcome variables (i.e., intention to leave the employer, intention to leave the MA profession, choosing MA profession again, and recommending MA profession to young people) were dichotomized, and logistic regression analyses were performed and limited to MAs in employment (n = 887). We found that increasing needs according to the categorized total needs score were associated with increasing odds of all occupational outcomes. Needs pertaining to working conditions and reward from the supervisor were the strongest determinants of MAs' consideration of leaving their employer or profession (Odds ratios: 1.55-2.61). In summary, our study identified unmet work-related intervention needs that are associated with unfavorable occupational outcomes. In light of staffing shortage in health care, the identified needs should be addressed to ensure that sufficient recruitment of junior staff in the profession of medical assistants remains feasible and that experienced staff is retained.


Texture and flavour memory in foods: an incidental learning experiment.
Memory plays a major role in the formation of food expectations. How accessible and how accurate is incidentally acquired and stored product information? In the present experiment the memory for variations in texture (and flavour) was tested with a new and ecologically valid method. Subjects (N=69: 35 women, 34 men, age 19-59 yrs) came to the institute before having had breakfast and received a breakfast of several items (including breakfast drinks, biscuits and pâté). Subsequently, during the day, they answered questions about their hunger feelings every hour and returned for a taste experiment at the end of the day. When unexpectedly confronted with a series of multiple samples of four texture variations of each of the breakfast items mentioned above, they had to indicate which of these variations they had eaten at breakfast. Signal detection measures showed that most subjects recognised the eaten versions well for all three of the food items. Women remembered better than men. Both men and women used an equally conservative criterion.


Structural insight into the unique binding properties of pyridylethanol(phenylethyl)amine inhibitor in human CYP51.
Sterol 14α-demethylase (CYP51) is the main drug target for the treatment of fungal infections. The discovery of new efficient fungal CYP51 inhibitors requires an understanding of the structural requirements for selectivity for the fungal over the human ortholog. In this study, a binding mode of the pyridylethanol(phenylethyl)amine type CYP51 inhibitor to the human ortholog was determined at the atomic level. We isolated and purified a full-length human CYP51. The inhibitor-specific binding and its conformational and dynamic properties were evaluated using UV-visible and NMR spectroscopy. Considering the experimental data in docking calculations and molecular dynamics simulations, the location of the inhibitor moieties and their interactions with the enzyme active site were determined. The inhibitor binds to the enzyme in two diastereomeric forms, which have a common location of aromatic ring moieties, while the less bulky propyl chain can adapt to various hydrophobic regions of the enzyme active site. The halogenated phenyl ring binds in the substrate access channel making numerous contacts with the hydrophobic side chains, and its interactions with the unconserved residues are especially informative. The results reveal the unique binding properties of the investigated inhibitor in comparison to the azoles and provide novel directions for the design of selective fungal inhibitors.


Inpatient and emergency room visits for adolescents and young adults with spina bifida living in South Carolina.
To compare emergency room (ER) and inpatient hospital (IP) use rates for persons with spina bifida (SB) to peers without SB, when transition from pediatric to adult health care is likely to occur; and to analyze those ER and IP rates by age, race, socioeconomic status, gender, and type of residential area. A retrospective cohort study. Secondary data analysis in South Carolina. We studied individuals who were between 15 and 24 years old and enrolled in the State Health Plan (SHP) or state Medicaid during the 2000-2010 study period. Individuals with SB were identified using ICD-9 billing codes (741.0, 741.9) in SHP, Medicaid, and hospital uniform billing (UB) data. ER and IP encounters were identified using UB data. Multivariable Generalized Estimating Equation (GEE) Poisson models were estimated to compare rates of ER and IP use among the SB group to the comparison group. Total ER rate and IP rate, in addition to cause-specific rates for ambulatory care sensitive conditions (ACSC) and other condition categories. We found higher rates of ER and IP use in persons with SB compared to the control group. Among individuals with SB, young adults (those 20-24 years old) had higher rates of ER use due to all ACSC (P = .023), other ACSC (P = .04), and urinary tract infections (UTI; P = .002) compared to adolescents (those 15-19 years old). Young adulthood is associated with increased ER use overall, as well as in specific condition categories (most notably UTI) in individuals 15-24 years old with SB. This association may be indicative of changing healthcare access as people with SB move from adolescent to adult health care, and/or physiologic changes during the age range studied.


Effects of exercise training on hepatic microsomal triglyceride transfer protein content in rats.
Microsomal triglyceride transfer protein (MTP) is a protein that exerts a central regulatory role in very-low-density lipoprotein (VLDL) assembly and secretion. The purpose of the study was to investigate the effects of an exercise-training program on hepatic content of MTP and its relation to hepatic VLDL-triglyceride (VLDL-TG) production in response to lipid infusion. Female rats either fed a standard (SD) or an obesity-induced high-fat (HF; 43% as energy) diet for 8 weeks were subdivided into sedentary (Sed) and trained (Tr) groups. Exercise training consisted of continuous running on a motor-driven rodent treadmill 5 times/week for 8 weeks. At the end of this period, all rats in the fasted state were intravenously infused with a 20% solution of Intralipid for 3 h followed by an injection of Triton WR1339 to block lipoprotein lipase. An additional control group consisting of Sed rats fed the SD diet was infused with saline (0.9% NaCl). Plasma TG accumulation was thereafter measured during 90 min to estimate VLDL-TG production. Under HF diet, hepatic MTP content and plasma TG accumulation after Triton blockade (thus reflecting VLDL-TG synthesis and secretion) were not changed in Sed rats, whereas liver TG content was highly increased (approximately 90%; p<0.01). On the other hand, training reduced liver MTP protein content in both SD (-18%) and HF (-23%) fed rats (p<0.05). Plasma VLDL-TG accumulation was also lower (p<0.05) in Tr than in Sed rats fed the HF diet. This effect was not observed in SD fed rats. Furthermore, the exercise training-induced decrease in VLDL-TG production in HF rats was associated with a decrease in liver TG levels. It is concluded that in addition to a reduction in liver TG content, exercise training reduces VLDL synthesis and/or secretion in HF fed rats probably via MTP regulation.


The prognostic values of signal transducers activators of transcription family in ovarian cancer.
Signal transducer and activator of transcription (STAT), a family of latent cytoplasmic transcription factors, are composed of seven identified members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6). STATs are associated with several biological processes such as cell proliferation, invasion, and metastasis in various cancer types. In addition, the STAT family has been well studied as a prognostic predictor for a considerable number of solid tumors. However, the prognostic value of the STAT family in ovarian cancer patients remains unclear. In our present study, we intend to access the prognostic roles of the STAT family in ovarian carcinoma through the 'Kaplan-Meier plotter' (KM plotter) online database, which collected gene expression data and survival information (overall survival (OS)) from a total of 1582 ovarian cancer patients. Our results show that high mRNA expression of STAT1, STAT4, STAT5a, STAT5b, and STAT6, are correlated to a better OS of ovarian cancer patients, especially the high level of STAT1 and STAT4 are significantly related to a favorable OS for serous ovarian cancer patients. We further accessed the prognostic roles of individual STATs in other clinicopathological features, such as pathological grades, clinical stages, and TP53 mutation, and found that these genes indicate a favorable prognosis especially for late stage, poor differentiation, and TP53 mutated ovarian cancer patients. In conclusion, these results suggest that the STAT family plays a significant prognostic role in ovarian carcinoma and individual STATs, except STAT2 and STAT3, may act as favorable prognostic markers in ovarian cancer.


Distribution and characteristics of androgen receptor (AR) in breast cancer among women in Addis Ababa, Ethiopia: A cross sectional study.
Evaluation of the role of androgen receptor (AR) in the biology of breast cancer is an emerging area of research. There are compelling evidences that AR expression may be used to further refine breast cancer molecular subtyping with prognostic and therapeutic implications. Many studies indicated co-expression of AR with the hormonal receptors in breast cancer has a favorable prognosis. AR is also investigated by many researchers as a potential therapeutic target in treatment of breast cancer. Studies on the frequency and distribution of AR in breast cancer among Africans is barely available. Given the heightened interest to understand its role in breast cancer, we determined AR expression and assessed its association with clinicopathological parameters among Ethiopian women. In this study, 112 newly diagnosed patient with invasive breast cancer at Tikur Anbessa Specialized Hospital were enrolled. Immunohistochemical assessment of AR, ER, PR, Ki67 and HER2 were performed using tissue microarrays (TMA) constructed from their primary tumor block. Out of the 112 participants, 91 (81%) were positive for AR expression and the remaining 21 participants (19%) were negative for AR expression. Expression of AR in ER+, HER2+ and TNBC cases were 93%, 83% and 48% respectively. Our study reveals AR is expressed in a significant number of breast cancers patients and this may indicate that breast cancers cases in Ethiopia have favorable prognosis and could benefit from progresses in AR targeted treatments. Since AR expression has important consequences on the prognosis and treatment of breast cancer, further studies with an increased number of participants is necessary to confirm our reports.


New trends in the diagnosis and therapy of acute cholangitis.
For a long time, acute cholangitis has been a difficult therapeutic problem, mostly due to the limited information about the jaundiced patient available from diagnostic investigations. The diagnostic precision of percutaneous transhepatic cholangiography in association with the great therapeutic possibilities of percutaneous transhepatic biliary drainage has solved this problem. The successful results obtained in 37 patients with acute cholangitis prove the value of this approach.


The TEAM (Trauma Evaluation and Management) course: medical student knowledge gains and retention in the USA versus Ghana.
Trauma and injury are significant contributors to the global burden of disease, with 5 million deaths and 250 million disability-adjusted life years lost in 2015. This burden is disproportionally borne by low- and middle-income countries (LMICs). Solutions are complex, but one area for improvement is basic trauma education. The American College of Surgeons has developed the Trauma Evaluation and Management (TEAM) course as an introduction to trauma care for medical students. We hypothesized that the TEAM course would be an effective educational program in LMICs and result in increased knowledge gains and retention similar to students in high-income countries (HICs). The TEAM course was taught and students evaluated at two sites, one LMIC (Ghana) and one HIC (USA), after obtaining approval from the HIC Institutional Review Board and medical schools at both sites. Participation was optional for all students and results were de-identified. The course was administered by a single educator for all sessions. Multiple-choice exams were given before and after the course, and again 6 months later. A total of 62 LMIC and 64 HIC students participated in the course and completed initial testing. Demographics for the two groups were similar, as was participant attrition over time. LMIC students started with a relative knowledge deficit, scoring lower on both pre-course and post-course tests than HIC students, but gained more knowledge during the initial teaching session. After 6 months, the LMIC students continued to improve, whereas the HIC students' knowledge had regressed. Most students recommended course expansion. The TEAM course is a useful tool to provide the basic principles of trauma care to students in LMICs, and should be expanded. Further study is needed to determine the impact of TEAM education on patient care in LMICs. Level III; Care Management.


Delivery of synergistic polyphenol combinations using biopolymer-based systems: Advances in physicochemical properties, stability and bioavailability.
When consumed at sufficiently high levels, polyphenols may provide health benefits, which is linked to their antidiabetic, antiinflamatory, antimicrobial, antioxidant, antitumor, and hypolipidemic properties. Moreover, certain polyphenol combinations exhibit synergistic effects when delivered together - the combined polyphenols have a higher biological activity than the sum of the individual ones. However, the commercial application of polyphenols as nutraceuticals is currently limited because of their poor solubility characteristics; instability when exposed to light, heat, and alkaline conditions; and, low and inconsistent oral bioavailability. Colloidal delivery systems are being developed to overcome these challenges. In this article, we review the design, fabrication, and utilization of food-grade biopolymer-based delivery systems for the encapsulation of one or more polyphenols. In particular, we focus on the creation of delivery systems constructed from edible proteins and polysaccharides. The optimization of biopolymer-based delivery systems may lead to the development of innovative polyphenol-enriched functional foods that can improve human health and wellbeing.


2-Thiohydantoin Moiety as a Novel Acceptor/Anchoring Group of Photosensitizers for Dye-Sensitized Solar Cells.
Very recently, we have reported the synthesis and evaluation of biological properties of new merocyanine dyes composed of triphenylamine moiety, π-aromatic spacer, and rhodanine/2-thiohydantoin-based moiety. Interestingly, 2-thiohydantoin has never been studied before as an electron-accepting/anchoring group for the dye-sensitized solar cells (DSSCs). In the presented study, we examined the applicability of 2-thiohydantoin, an analog of rhodanine, in DSSC technology. The research included theoretical calculations, electrochemical measurements, optical characterization, and tests of the solar cells. As a result, we proved that 2-thiohydantoin might be considered as an acceptor/anchoring group since all the compounds examined in this study were active. The most efficient device showed power conversion efficiency of 2.59%, which is a promising value for molecules of such a simple structure. It was found that the cells' performances were mainly attributed to the dye loading and the ICT molecular absorption coefficients, both affected by the differences in the chemical structure of the dyes. Moreover, the effect of the aromatic spacer size and the introduction of carboxymethyl co-anchoring group on photovoltaic properties was observed and discussed.


Reverse-Flow Lateral Tarsal Island Flap for Covering the Great Toe Donor Site of Wraparound Flap.
Coverage of the great toe donor site of wraparound flap remains a challenge. This report presents the results of using an innervated pedicled reverse-flow lateral tarsal island flap for covering the great toe donor site of wraparound flap. Between 2005 and 2010, 11 reverse-flow lateral tarsal island flaps were used to cover the great toe donor site of wraparound flap in 11 patients. This pedicled flap designed on the lateral tarsal area of foot was based distally on the dorsalis pedis artery; the lateral dorsal pedal cutaneous nerve was incorporated into the reverse-flow lateral tarsal island flap and coapted with the first plantar digital nerve. The donor sites of reverse-flow lateral tarsal island flap were covered with inguinal full-thickness skin grafts. All flaps achieved primary healing except for two that suffered from mild venous insufficiency which was managed by conservative intervention. All skin grafts covering the donor site of reverse-flow lateral tarsal island flap healed uneventfully. The mean follow-up was 24 months (range, 18-48 months). The mean hallux metatarsophalangeal-interphalangeal scale score was 92 points (range, 85-97 points) at 6 months postoperatively. The static 2-point discrimination of the reverse-flow lateral tarsal island flap ranged from 6 to 14 mm (mean 10 mm). None of the patients were restricted in standing or walking during follow-up. The reverse-flow lateral tarsal island flap based distally on the dorsalis pedis artery has a constant pedicle that is sufficiently long. This innervated pedicle flap is a reliable option to cover the great toe donor site of wraparound flap with satisfactory functional and cosmetic results and acceptable donor site morbidity.


Synthetic studies toward amphidinolide B1: synthesis of the C9-C26 fragment.
[reaction: see text] The synthesis of the C9-C26 portion of amphidinolide B1 is described. A Fleming allylation followed by elimination was employed for the construction of the C13-C15 diene portion. Sharpless asymmetric dihydroxylation was utilized for regioselective functionalization of a styrene-derived alkene, in the presence of the C13-C15 diene functionality. A highly diastereoselective aldol reaction was developed to establish the C18 stereochemistry.


Palladium-Catalyzed Direct Annulation of Benzoic Acids with Phenols to Synthesize Dibenzopyranones.
Direct annulation of benzoic acids with phenols via palladium-catalyzed oxidative coupling is reported. Readily available and inexpensive starting materials were used in this novel method to synthesize highly valuable and useful dibenzopyranone scaffolds. Broad substrate scope and simple operation make this method potentially practical. Preliminary mechanistic studies were conducted to understand this chemistry and inspire new designs of oxidative coupling of different functionalized arenes.


Reciprocal role of hBD2 and hBD3 on the adaptive immune response by measuring T lymphocyte proliferation in terms of CD4 and CCR6 expression.
Background Human β-defensins (hBD2 and hBD3) are small cationic antimicrobial peptides of innate immune system which can act as a barrier against the majority of pathogens, contributing to the host immune defence. Objective The aim of study is to determine whether hBD2 and hBD3 play a role in development and proliferation of human effector CD4 T cells or not. Furthermore, if enhanced proliferation is observed in the presence of hBD2 and hBD3, these data will demonstrate whether chemokine receptor type 6 (CCR6) is required to be present for this activity to occur. Methods In this study, we examined the effect of hBD2 and hBD3 on CD4+ T cell proliferation in CCR6+ and CCR6- T cells through co-culture of peripheral blood mononuclear cells with anti-CD3 and anti-CD28 stimulation in the presence or absence of hBD2 and hBD3. Proliferation was assessed using flow cytometry. Results It was demonstrated that, co-culture with hBD2 and hBD3 led to up-regulation of CD4+ T cell proliferation after 72 h whereas, CD4+ T cell proliferation was suppressed after 96 h. On the other hand, CCR6- and CCR6+ T cell proliferation was up-regulated after 72 h. But, CCR6+ only was down-regulated in the second cycle in the presence of hBD3. In contrast, after 96 h CCR6+ and CCR6- T cell proliferation was decreased. Conclusion Collectively, our data indicated that hBD2 and hBD3 play a positive and negative regulatory role in development and proliferation of human effector CD4+ T cells which is essential for optimal adaptive immune responses and the control of immunopathology.


Single-pass BPM system of the Photon Factory storage ring.
At the 2.5 GeV ring of the Photon Factory, a single-pass beam-position monitor (BPM) system is being prepared for the storage ring and the beam transport line. In the storage ring, the injected beam position during the first several turns can be measured with a single injection pulse. The BPM system has an adequate performance, useful for the commissioning of the new low-emittance lattice. Several stripline BPMs are being installed in the beam transport line. The continuous monitoring of the orbit in the beam transport line will be useful for the stabilization of the injection energy as well as the injection beam orbit.


Demographic Comparison of Burn Emergency Only Visits and Admissions in an Urban Burn Center.
There are few publications about demographics of Emergency Department (ED) burn patient visits. The purpose of this study was to compare ED only burn patients with admitted patients in an urban burn center. This was a retrospective review (1999 to 2014) of a burn unit patient registry. Patients were seen either in the Emergency Room or Trauma Bay (ED-TB) by staff, who determined whether the patient required admission or not. During this period, of the 5936 burn injury ED-TB encounters, there were 3754 (63%) admissions and 2182 (37%) ED-TB only (evaluation and discharge) visits. The median age was 30 years, and the %TBSA in the ED-TB only versus admitted patients was 1% vs 4% TBSA, P < .0001. Both groups had mainly scalding injuries in the kitchen. The majority of the ED-TB only patients presented with upper extremity burns (40%), whereas admitted patients had burns in multiple areas (49%). Most of the ED-TB only patients (73%) came to the hospital themselves, 23% were transferred from other hospitals, and 2% each, direct from the scene and clinic. In contrast, 53% of admitted patients were transferred from other hospitals, 29% came in on their own, and 11% were brought in direct from the scene, or from the burn clinic (7%), P = .0001. This review suggests that the main reason for non-admission of ED-TB only patients was the severity of injury; ED-TB only patients had a significantly less severe %TBSA (P < .0001), and fewer comorbidities compared to admitted patients.


Acidic pH promotes dimerization of Bcl-2 family proteins.
Several members of the apoptosis-regulating Bcl-2 family of proteins can homo- or heterodimerize with each other at neutral pH and can also form ion channels in synthetic membranes at low pH. The effects of low pH on dimerization among these proteins, however, have not heretofore been examined. Surface plasmon resonance was used to examine the kinetics of dimerization as a function of pH between the anti-apoptotic protein Bcl-XL (applied in the mobile phase) and three other members of the Bcl-2 family: Bcl-2, Bax, and Bid (immobilized on biosensor chips). In all cases, the relative affinity of dimerization was substantially increased at pH 4.0 compared to pH 7.0-7.4, ranging from a approximately 10-fold enhancement for Bcl-XL/Bcl-XL homodimers to >60-fold for Bcl-XL/Bid heterodimers. Comparison of the apparent association (ka) and dissociation (kd) rates at neutral and acidic pH revealed that the major contributor to increased affinity at low pH was a decreased rate of dimer dissociation. Thus, low pH stabilizes homo- and heterodimeric complexes comprised of Bcl-XL and these other Bcl-2 family proteins. At pH 4.0, the circular dichroism spectra of Bcl-XL and Bax were essentially unchanged relative to pH 7.0-7.4, indicating a complete retention of alpha-helical secondary structure at low pH and excluding gross denaturation of the proteins. Size-exclusion chromatography and bisANS (4,4'-dianilino-1, 1'-binaphthyl-5,5'-disulfonic acid) labeling studies provided indirect evidence that Bcl-XL may undergo conformational changes at low pH. The findings are discussed with respect to the mechanisms of ion-channel formation by Bcl-2 family proteins and the putative molten globule state that has been proposed for these and structurally similar proteins.


Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB.
Despite intensive efforts in recent years, a curative therapy for cutaneous T-cell lymphoma (CTCL) has not yet been developed. Therefore, the establishment of new therapeutic approaches with higher efficacy rates and milder side effects is strongly desired. A characteristic feature of the malignant T-cell population in CTCL is resistance toward cell death resulting from constitutive NF-κB activation. Therefore, NF-κB-dependent cell death resistance represents an interesting therapeutic target in CTCL because an NF-κB-directed therapy would leave bystander T cells widely unaffected. We investigated the effects of dimethyl fumarate (DMF) on CTCL cells in vitro and in vivo. DMF induced cell death in primary patient-derived CD4(+) cells and CTCL cell lines, but hardly in T cells from healthy donors. DMF-induced cell death was linked specifically to NF-κB inhibition. To study the impact of DMF in vivo, we developed 2 CTCL xenograft mouse models with different cutaneous localizations of the T-cell infiltrate. DMF treatment delayed the growth of CTCL tumors and prevented formation of distant metastases. In addition, DMF induced increased cell death in primary CTCL tumors and in liver metastases. In summary, DMF treatment represents a remarkable therapeutic option in CTCL because it restores CTCL apoptosis in vitro and in preclinical models in vivo and prevents spreading of the disease to distant sites. DMF treatment is of particular promise in CTCL because DMF is already in successful clinical use in the treatment of psoriasis and multiple sclerosis allowing fast translation into clinical studies in CTCL.


Quantifying the epidemic spread of Ebola virus (EBOV) in Sierra Leone using phylodynamics.
Measuring epidemic parameters early in an outbreak is essential to inform control efforts. Using the viral genome sequence and collection date from 78 infections in the 2014 Ebola virus outbreak in Sierra Leone, we estimate key epidemiological parameters such as infectious period duration (approximately 71 hours) and date of the first case in Sierra Leone (approximately April 25th). We also estimate the effective reproduction number, Re, (approximately 1.26), which is the number of secondary infections effectively caused by an infected individual and accounts for public health control measures. This study illustrates that phylodynamics methods, applied during the initial phase of an outbreak on fewer and more easily attainable data, can yield similar estimates to count-based epidemiological studies.


A Bayesian network analysis of psychosocial risk and protective factors for suicidal ideation.
The aim of this study was to investigate and model the interactions between a range of risk and protective factors for suicidal ideation using general population data collected during the critical phase of the COVID-19 pandemic. Bayesian network analyses were applied to cross-sectional data collected 1 month after the COVID-19 lockdown measures were implemented in Austria and the United Kingdom. In nationally representative samples (n = 1,005 Austria; n = 1,006 UK), sociodemographic features and a multi-domain battery of health, wellbeing and quality of life (QOL) measures were completed. Predictive accuracy was examined using the area under the curve (AUC) within-sample (country) and out-of-sample. The AUC of the Bayesian network models were ≥ 0.84 within-sample and ≥0.79 out-of-sample, explaining close to 50% of variability in suicidal ideation. In total, 15 interrelated risk and protective factors were identified. Seven of these factors were replicated in both countries: depressive symptoms, loneliness, anxiety symptoms, self-efficacy, resilience, QOL physical health, and QOL living environment. Bayesian network models had high predictive accuracy. Several psychosocial risk and protective factors have complex interrelationships that influence suicidal ideation. It is possible to predict suicidal risk with high accuracy using this information.


A novel triple-color detection procedure for brightfield microscopy, combining in situ hybridization with immunocytochemistry.
We describe a fast light microscopic procedure for the simultaneous enzyme cytochemical detection of three different DNA target sequences in contrasting colors in both interphase and metaphase cell preparations. Chromosome-specific DNA probes labeled with either biotin, digoxygenin, or fluorescein were hybridized as a mixture and detected clearly and accurately by precipitates of the horseradish peroxidase-diaminobenzidine (PO-DAB, brown color), alkaline phosphatase-Fast Red (APase-Fast Red, red color), or horseradish peroxidase-tetramethylbenzidine (PO-TMB, green color) reaction, respectively. The PO-TMB reaction product was stabilized effectively by the addition of sodium tungstate to the reaction mixture, thus making the PO-TMB reaction now generally applicable to in situ hybridization (ISH). To avoid mixing of the precipitates of the two PO reactions used in the triple-color ISH method, the first detected PO activity was always completely inactivated by a mild acid treatment before the second one was applied. Finally, the cell preparations were embedded in a thin protein layer cross-linked by formaldehyde to ensure permanent stabilization of the enzyme reaction products and optimal visualization of color contrast. The triple-color ISH detection procedure could be combined with beta-galactosidase-5-bromo-4-chloro-3-indolyl-beta- D-galactoside (beta-Gal-BCIG) immunocytochemistry (ICC), leading to the simultaneous localization of multiple DNA targets and a protein target in the same cell. The described procedure may therefore be a valuable tool in the areas of cytogenetics, cell biology, and molecular pathology.


Fetal organ dosimetry for the Techa River and Ozyorsk offspring cohorts, part 1: a Urals-based series of fetal computational phantoms.
The European Union's SOLO (Epidemiological Studies of Exposed Southern Urals Populations) project aims to improve understanding of cancer risks associated with chronic in utero radiation exposure. A comprehensive series of hybrid computational fetal phantoms was previously developed at the University of Florida in order to provide the SOLO project with the capability of computationally simulating and quantifying radiation exposures to individual fetal bones and soft tissue organs. To improve harmonization between the SOLO fetal biokinetic models and the computational phantoms, a subset of those phantoms was systematically modified to create a novel series of phantoms matching anatomical data representing Russian fetal biometry in the Southern Urals. Using previously established modeling techniques, eight computational Urals-based phantoms aged 8, 12, 18, 22, 26, 30, 34, and 38 weeks post-conception were constructed to match appropriate age-dependent femur lengths, biparietal diameters, individual bone masses and whole-body masses. Bone and soft tissue organ mass differences between the common ages of the subset of UF phantom series and the Urals-based phantom series illustrated the need for improved understanding of fetal bone densities as a critical parameter of computational phantom development. In anticipation for SOLO radiation dosimetry studies involving the developing fetus and pregnant female, the completed phantom series was successfully converted to a cuboidal voxel format easily interpreted by radiation transport software.


Synthesis of chitosan-stabilized polymer dispersions, capsules, and chitosan grafting products via miniemulsion.
The potential of chitosan as an emulsion stabilizer is combined with the miniemulsion technique to generate oil droplets, hollow capsules, and latex particles in the diameter range of 100-300 nm carrying a functional biopolymer surface. It turned out that chitosan alone, independent of its molecular weight, is just moderately efficient, which is speculatively attributed to its stiff polysaccharide structure. The addition of biocompatible costabilizers with higher flexibility either to the oil phase or to the water phase, such as Jeffamine or Gluadin (a peptide), eliminates these deficiencies, and very small nanocapsules made of biopolymer hybrids can be obtained. NMR analysis shows that the costabilizer is effectively grafted/cross-linked to the chitosan which makes the miniemulsion route also effective for the modification of hard-to-handle, amphiphilic biopolymers either from the water or from the oil phase.


Fine structure of the asexual stages of Plasmodium elongatum.
Plasmodium elongatum, an avian malarial parasite, differs from other such parasites by infecting both the circulating red blood cells and the hematopoietic cells. The exoerythrocytic development of P. elongatum occurs mainly in these red cell precursors. The fine structure of the asexual stages of P. elongatum has been studied in the bone marrow and peripheral blood of canaries and compared with that of the asexual stages of other avian malarial parasites. With minor differences, the merozoites of P. elongatum possess the same organelles as those in the exoerythrocytic merozoites of P. fallax and the erythrocytic stages of P. cathemerium, P. lophurae, P. fallax, and P. gallinaceum. The developmental sequence is also essentially similar to that of other avian malarial parasites, in that upon entry into a new host cell, the dedifferentiation, growth, and redifferentiation phases take place. However, we have found some important differences in the feeding mechanism of P. elongatum. The cytostome is involved in the ingestion of host cell cytoplasm in both exoerythrocytic and erythrocytic stages, in contrast to P. fallax, in which the cytostome is inactive in the exoerythrocytic stages. In P. elongatum, host cell cytoplasm is ingested through the cytostome, and "boluses" are formed and incorporated into a large digestive vacuole. Subsequently, the digestion of the boluses takes place in this digestive vacuole. Thus, in regard to the function of the cytostome, the exoerythrocytic stages of P. elongatum appear to be closely related to the erythrocytic stage which has a feeding mechanism similar to that of the erythrocytic stage of other avian malarial parasites.


Combustion synthesis of porous biomaterials.
This article discusses the unique material manufacturing process of self-propagating high temperature synthesis (SHS) as applied to the making of porous biomaterials. Porous materials have long been considered as the first step toward in-vivo bone tissue engineering and the creation of patient life-time implants. The authors have approached this challenge by utilizing combustion synthesis, to create novel materials such as NiTi + TiC as well as porous forms of materials that are commonly accepted for biomedical applications such as tricalcium phosphate and hydroxyapatite. In the SHS product, physico-chemical properties are controlled by, but not limited to, reactant stoichiometry; green density; particle size of the reactant mix; use or presence of a gasifying agent; heating rate of the reactants and gravity. By balancing these parameters, the energy of the reaction is controlled to create the desired product stoichiometry, porosity, and mechanical properties. SHS provides a means to rapidly manufacture materials, saving time and production costs as well as enabling the synthesis of custom devices through the use of individual molds. Mold materials can range from graphite to paper or paper machete. Combustion synthesis offers a method for the rapid manufacture of affordable, individual biomedical devices that will reduce patient recovery time.


Dynamic contrast-enhanced MRI of prostate cancer at 3 T: a study of pharmacokinetic parameters.
The objectives of our study were to determine whether dynamic contrast-enhanced MRI performed at 3 T and analyzed using a pharmacokinetic model improves the diagnostic performance of MRI for the detection of prostate cancer compared with conventional T2-weighted imaging, and to determine which pharmacokinetic parameters are useful in diagnosing prostate cancer. This prospective study included 50 consecutive patients with biopsy-proven prostate cancer who underwent imaging of the prostate on a 3-T scanner with a combination of a sensitivity-encoding (SENSE) cardiac coil and an endorectal coil. Scans were obtained at least 5 weeks after biopsy. T2-weighted turbo spin-echo images were obtained in three planes, and dynamic contrast-enhanced images were acquired during a single-dose bolus injection of gadopentetate dimeglumine (0.1 mmol/kg). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated for T2-weighted and dynamic contrast-enhanced MRI. The following pharmacokinetic modeling parameters were determined and compared for cancer, inflammation, and healthy peripheral zone: K(trans) (forward volume transfer constant), k(ep) (reverse reflux rate constant between extracellular space and plasma), v(e) (the fractional volume of extracellular space per unit volume of tissue), and the area under the gadolinium concentration curve (AUGC) in the first 90 seconds after injection. Pathologically confirmed cancers in the peripheral zone of the prostate were characterized by their low signal intensity on T2-weighted scans and by their early enhancement, early washout, or both on dynamic contrast-enhanced MR images. The overall sensitivity, specificity, PPV, and NPV of T2-weighted imaging were 94%, 37%, 50%, and 89%, respectively. The sensitivity, specificity, PPV, and NPV of dynamic contrast-enhanced MRI were 73%, 88%, 75%, and 75%, respectively. K(trans), k(ep), and AUGC were significantly higher (p < 0.001) in cancer than in normal peripheral zone. The ve parameter was not significantly associated with prostate cancer. MRI of the prostate performed at 3 T using an endorectal coil produces high-quality T2-weighted images; however, specificity for prostate cancer is improved by also performing dynamic contrast-enhanced MRI and using pharmacokinetic parameters, particularly K(trans) and k(ep), for analysis. These results are comparable to published results at 1.5 T.


Silver-catalyzed C-H trifluoromethylation of arenes using trifluoroacetic acid as the trifluoromethylating reagent.
Direct trifluoromethylation of arenes using TFA as the trifluoromethylating reagent was achieved with Ag as the catalyst. This reaction not only provides a new protocol for aryl C-H trifluoromethylation, but the generation of CF3· from TFA may prove useful in other contexts and could potentially be extended to other trifluoromethylation reactions.


Collision energy alteration during mass spectrometric acquisition is essential to ensure unbiased metabolomic analysis.
Metabolomics entails identification and quantification of all metabolites within a biological system with a given physiological status; as such, it should be unbiased. A variety of techniques are used to measure the metabolite content of living systems, and results differ with the mode of data acquisition and output generation. LC-MS is one of many techniques that has been used to study the metabolomes of different organisms but, although used extensively, it does not provide a complete metabolic picture. Recent developments in technology, for example the introduction of UPLC-ESI-MS, have, however, seen LC-MS become the preferred technique for metabolomics. Here, we show that when MS settings are varied in UPLC-ESI-MS, different metabolite profiles result from the same sample. During use of a Synapt UPLC-high definition MS instrument, the collision energy was continually altered (3, 10, 20, and 30 eV) during MS acquisition. PCA and OPLS-DA analysis of the generated UPLC-MS data of metabolites extracted from elicited tobacco cells revealed different clustering and different distribution patterns. As expected, ion abundance decreases with increasing collision energy, but, more importantly, results in unique multivariate data patterns from the same samples. Our findings suggest that different collision energy settings should be investigated during MS data acquisition because these can contribute to coverage of a wider range of the metabolome by UPLC-ESI-MS and prevent biased results.


Immunological response against allogeneic chondrocytes transplanted into joint surface defects in rats.
Rat chondrocytes isolated from the articular-epiphyseal cartilage complex were transplanted into defects prepared in articular cartilage and subchondral bone. Transplants were taken for examination after 3 and 8 wk. Cartilage formed by syngeneic chondrocytes did not evoke formation of infiltrations. Contrary to that, in the vicinity of cartilage produced by allogeneic chondrocytes numerous infiltrating cells were present and cartilage resorption could be observed. Cyclosporine-A (CsA) treatment of recipients of allogeneic chondrocytes only partially suppressed accumulation of infiltrating cells and matrix resorption. Antichondrocyte immune response of chondrocyte graft recipients was studied by evaluation of spleen mononuclear cells (SMC) stimulation in mixed splenocyte-chondrocyte cultures and by evaluation of antichondrocyte cytotoxic antibodies. No difference in stimulation of SMC from intact rats by syngeneic and allogeneic chondrocytes was observed. Stimulation by allogeneic chondrocytes was slightly but significantly higher in recipients of syngeneic grafts. SMC of allogenic chondrocyte recipients were strongly stimulated by allogeneic chondrocytes. This response was absent in recipients treated with CsA. Spontaneous antichondrocyte cytotoxic antibody activity was detected in intact rats and in recipients of syngeneic grafts. In recipients of allogeneic chondrocytes the antibody response against allogeneic chondrocytes was raised but was statistically not significant owing to the considerable variation in the level of spontaneously occurring antichondrocyte antibodies.


Neutralizing activity against Omicron BA.5 after tixagevimab/cilgavimab administration comparable to those after Omicron BA.1/BA.2 breakthrough infections.
The effect of tixagevimab/cilgavimab (Evusheld™; AstraZeneca, UK) should be evaluated in the context of concurrent outbreak situations. For serologic investigation of tixagevimab/cilgavimab during the BA.5 outbreak period, sera of immunocompromised (IC) hosts sampled before and one month after tixagevimab/cilgavimab administration and those of healthcare workers (HCWs) sampled one month after a 3rd shot of COVID-19 vaccines, five months after BA.1/BA.2 breakthrough infection (BI), and one month after BA.5 BI were investigated. Semi-quantitative anti-spike protein antibody (Sab) test and plaque reduction neutralizing test (PRNT) against BA.5 were performed. A total of 19 IC hosts (five received tixagevimab/cilgavimab 300 mg and 14 received 600 mg) and 41 HCWs (21 experienced BA.1/BA.2 BI and 20 experienced BA.5 BI) were evaluated. Baseline characteristics did not differ significantly between IC hosts and HCWs except for age and hypertension. Sab significantly increased after tixagevimab/cilgavimab administration (median 130.2 BAU/mL before tixagevimab/cilgavimab, 5,665.8 BAU/mL after 300 mg, and 10,217 BAU/mL after 600 mg; both P < 0.001). Sab of one month after the 3rd shot (12,144.2 BAU/mL) or five months after BA.1/BA.2 BI (10,455.8 BAU/mL) were comparable with that of tixagevimab/cilgavimab 600 mg, while Sab of one month after BA.5 BI were significantly higher (22,216.0 BAU/mL; P < 0.001). BA.5 PRNT ND50 significantly increased after tixagevimab/cilgavimab administration (median ND50 29.6 before tixagevimab/cilgavimab, 170.8 after 300 mg, and 298.5 after 600 mg; both P < 0.001). The ND50 after tixagevimab/cilgavimab 600 mg was comparable to those of five months after BA.1 BI (ND50 200.9) while ND50 of one month after the 3rd shot was significantly lower (ND50 107.6; P = 0.019). The ND50 of one month after BA.5 BI (ND50 1,272.5) was highest among tested groups, but statistical difference was not noticed with tixagevimab/cilgavimab 600 mg. Tixagevimab/cilgavimab provided a comparable neutralizing activity against the BA.5 with a healthy adult population who were vaccinated with a 3rd shot and experienced BA.1/BA.2 BI.


Excluding Clinically Significant Bacteremia by 24 Hours in Otherwise Well Febrile Children Younger Than 16 Years: A Study of More Than 50,000 Blood Cultures.
In febrile children given empiric parenteral antibiotics, guidelines advise provisional reporting of negative blood cultures and antibiotic review after 36 hours incubation for neonates and 48 hours for older children. Following improvements in culture processing and childhood vaccination, we revisited this important clinical topic, assessing time to exclude clinically significant bacteremia in well-appearing febrile children with no comorbidities or features of sepsis. We analyzed the results of all 53,276 pediatric blood cultures taken during an 8-year period at a UK hospital. 1308 (2.5%) cultures were positive, of which 333 (25.5%) grew pathogens typically associated with clinically significant bacteremia. The remaining 975 (74.5%) grew organisms associated with contaminated culture, or with opportunistic infection only in children with relevant risk factors. Time to positivity (TTP) from incubation was significantly shorter for the 333 definite pathogens than the 975 contaminating/opportunistic organisms, with 92% of definite pathogens identified by 24 hours incubation. Only 3 of all definite pathogens were identified after 24 hours in children otherwise eligible for discharge at 24 hours. There was no significant difference in TTP for definite pathogens between neonates and older children. Median time from specimen collection to incubation was 3 hours. Clinically significant bacteremia can be excluded by 24 hours incubation in well-appearing febrile children with no comorbidities or features of sepsis. This is the largest dataset of its kind, and the second to compare neonates and older children. Our findings may inform future guidelines, facilitating earlier antibiotic review and discharge.


Enhanced Low-Temperature Hydrogen Storage in Nanoporous Ni-Based Alloy Supported LiBH4.
To reveal the synergistic effect of nanoconfinement and metallic catalysis on the hydrogen storage properties of LiBH4, the nanoporous Ni-based alloy (np-Ni) was prepared herein by dealloying of the Mn70Ni30 alloy in (NH4)2SO4 solution, and then LiBH4 was loaded into np-Ni to construct the LiBH4/np-Ni hydrogen storage system using wet impregnation. It was found that dehydrogenation of the LiBH4/np-Ni (1:5) system starts at around 70°C and ends before 400°C, with ~11.9 wt.% of hydrogen desorbed. The apparent dehydrogenation activation energy for the LiBH4/np-Ni (1:5) system was remarkable decreased to about 11.4 kJ/mol. After rehydrogenation at 450°C under 8 MPa hydrogen pressure, ~8.2 wt.% of hydrogen can be released from about 60°C upon second dehydrogenation. These obtained results would provide an efficient strategy for improving the hydrogen storage properties of other metal borohydrides.


[Primary volvulus of the small intestine without malrotation. Apropos of 7 cases].
We report seven cases of complete volvulus of the small bowel without malrotation seen from 1973 through 1986. The clinical setting is always the same in this condition: the infant exhibits no clinical anomalies during the symptom-free interval between birth and the volvulus (4 h to 35 d, m = 7 d in our series). Onset is extremely sudden, with a complete, proximal obstruction, early and abundant passage of blood per rectum, and above all a severe shock that fails to respond to resuscitation. Roentgenograms contribute little to the diagnosis and surgery should never be delayed to perform complementary investigations of any kind. Indeed, the only effective treatment is unwinding the volvulus within the first six hours following onset, for beyond that time irreversible necrosis of the entire small bowel and occasionally colon occurs. Five infants died because they were seen too late and operated on 36 hours on average after the onset of symptoms. The two survivors had an early operation that prevented total necrosis of the small bowel. However, this pattern seems to vary according to the degree of cecum anchorage: a fixed cecum results in a very tight volvulus with complete, early ischemia and usually irreversible necrosis of the small bowel beyond the sixth hour (9/9 published cases); an even slightly mobile cecum results in a looser volvulus, with less severe ischemia, more delayed necrosis, and a possibility of complete recovery (5/6 published cases).(ABSTRACT TRUNCATED AT 250 WORDS)


Canalisation and plasticity on the developmental manifold of Caenorhabditis elegans.
How do the same mechanisms that faithfully regenerate complex developmental programmes in spite of environmental and genetic perturbations also allow responsiveness to environmental signals, adaptation and genetic evolution? Using the nematode Caenorhabditis elegans as a model, we explore the phenotypic space of growth and development in various genetic and environmental contexts. Our data are growth curves and developmental parameters obtained by automated microscopy. Using these, we show that among the traits that make up the developmental space, correlations within a particular context are predictive of correlations among different contexts. Furthermore, we find that the developmental variability of this animal can be captured on a relatively low-dimensional phenotypic manifold and that on this manifold, genetic and environmental contributions to plasticity can be deconvolved independently. Our perspective offers a new way of understanding the relationship between robustness and flexibility in complex systems, suggesting that projection and concentration of dimension can naturally align these forces as complementary rather than competing.


Risks associated with conversion of stable patients after liver transplantation to the microemulsion formulation of cyclosporine.
Neoral is a microemulsion formulation of cyclosporine that has a better pharmacokinetic profile than the standard formulation (Sandimmune). To prove the safety of converting stable liver transplant patients from Sandimmune to Neoral, we conducted a prospective trial involving 54 patients. The average time from transplantation to conversion was 48.5+/-21.6 months. Thirty of 54 patients (55%) required a dose reduction during the study for various reasons. Five of 30 patients had the first dose reduction because of increased levels of cyclosporine. Seven patients required more than one dose reduction. Sixteen patients suffered serious adverse events. Six patients had a biopsy-proven rejection. Four of 6 patients had trough cyclosporine levels within 20% of baseline value immediately before developing rejection. Converting patients from the standard formulation to the microemulsion formulation of cyclosporine seems to expose stable patients to unnecessary risks.


Structural variations of lignin macromolecule from different growth years of Triploid of Populus tomentosa Carr.
To better understand the variations of structural characteristics of lignin macromolecules during different growth years of Triploid of Populus tomentosa Carr, a novel lignin isolation procedure based on double ball-milling and enzymatic hydrolysis (DEL) was proposed in this study. The morphological distributions of lignin in the plant cell wall of these poplar wood samples were monitored by Confocal Raman Microscopy (CRM). The ultrahigh yields (105.1%-111.2%) of DELs were significantly higher than those (24.4-31.8%) of corresponding cellulolytic enzyme lignins (CELs). DELs and CELs were elaborately characterized by HPAEC, GPC, 2D-HSQC NMR and 31P NMR techniques, and NMR results showed that DEL samples possess similar structural features as compared to CEL counterparts except for the decreased S/G ratio and p-hydroxybenzoate (PB) as well as increased p-hydroxyphenyl units (H). There are no obvious differences in the structural characteristics except for high contents of PB and H units in DEL-1, as well as high S/G ratio and β-O-4' linkages in DEL-5. It is believed that the DEL proposed in the present study can be used for characterizing the entire structural features of lignin macromolecules in the plant cell wall of different kinds of lignocellulosic biomass.


Psychiatry in the emergency room: clinical experience in Perugia.
We examined all psychiatric consultations carried out over 3 years at the Emergency Room (ER) of the hospital of Perugia, with the aim of describing the epidemiologic characteristics of patients with any psychiatric illness and their management. We also assessed the distribution of psychiatric emergencies over this period of observation. We recruited patients consecutively admitted to the ER, between June the 20th 2011 and June the 20th 2014, for which a psychiatric consultation was required. We analysed socio-demographic and clinical data as well as the type of long-range plan after discharge. Continuous variables were presented as means and standard deviations. Categorical variables were presented as number and percentages. For comparing the means we used the Student's t-test. For analyzing the association between categorical variables we performed Pearson's chi-squared test or the Fisher's exact test where appropriate. We considered significant test results with p<0.05. The post-hoc analyses were carried out by means of standardized Pearson residuals, in order to assess the significance of the cell-wise divergences from homogeneity. Spearman's correlations were computed for reasons for a psychiatric consultation request across months. Multinomial logistics regression model was used for analyzing the variability of the reasons for the admission to the ER for the 12 months. Statistical analyses were performed using the R software v 3.1. Neurotic, stress-related and somatoform disorders were the most represented. The most frequent approach to patients with psychiatric complaints did not imply the use of psychopharmacological treatments or coercive interventions. No particular seasonality of psychopathology was observed. ERs may represent the place where the first psychiatric visit occurs and a point of reference for the chronic patients. It can also represent an opportunity for further examination of organic comorbidity.


Chrono-modulated effects of external stressors on oxidative stress and damage in humans: A scoping review on night shift work.
Oxidative stress and tissue damage (OSD) play a pivotal role as an early-stage process in chronic disease pathogenesis. However, there has been little research to better understand the temporal (χρόνος[chronos]) dimensions of OSD process associated with environmental (non-genetic, including behaviors/lifestyle) and/or occupational stressors, like night shift work. OSD processes have recently attracted attention in relation to time-resolved external stressor trajectories in personalized medicine (prevention) initiatives, as they seem to interact with circadian clock systems towards the improved delineation of the early stages of (chronic) disease process. This work critically reviewed human studies targeting the temporal dynamics of OSD and circadian clock system's activity in response to environmental/occupational stressors; the case of night shift work was examined. Being a key stressor influencing OSD processes and circadian rhythm, night shift work was evaluated as part of a scoping review of research in OSD, including inflammatory and metabolic processes to determine the extent of OSD research undertaken in human populations, methodologies, tools and biomarkers used and the extent that the temporal dimensions of exposure and biological effect(s) were accounted for. Online databases were searched for papers published from 2000 onwards, resulting in the selection of 53 original publications. The majority of studies (n = 41) took place in occupational settings, while the rest were conducted in the general population or patient groups. Most occupational studies targeted outcomes of oxidative stress/damage (n = 19), followed by the combination of OSD with inflammatory response (n = 10), and studies focused on metabolic outcomes (n = 12). Only a minor fraction of the studies measured biomarkers related to circadian rhythm, such as, melatonin, its metabolite, or cortisol. Night shift work was associated with select biomarkers of OSD and inflammation, albeit with mixed results. Although much progress in delineating the biological mechanisms of OSD process has been made, an equally thorough investigation on the temporal trajectory of OSD processes as triggered by environmental/occupational stressors in human studies has yet to fully evolve.


The Bright Futures Training Intervention Project: implementing systems to support preventive and developmental services in practice.
The objectives of this study were to assess the feasibility of implementing a bundle of strategies to facilitate the use of Bright Futures recommendations and to evaluate the effectiveness of a modified learning collaborative in improving preventive and developmental care. Fifteen pediatric primary care practices from 9 states participated in a 9-month learning collaborative. Support to practices included a toolkit, 2 workshops, training in quality-improvement methods, monthly conference calls and data feedback, and a listserv moderated by faculty. Aggregated medical chart reviews and practice self-assessments on 6 key office system components were compared before and after the intervention. Office system changes most frequently adopted were use of recall/reminder systems (87%), a checklist to link to community resources (80%), and systematic identification of children with special health care needs (80%). From baseline to follow-up, increases were observed in the use of recall/reminder systems, the proportion of children's charts that had a preventive services prompting system, and the families who were asked about special health care needs. Of 21 possible office system components, the median number used increased from 10 to 15. Comparing scores between baseline and follow-up for each practice site, the change was significant. Teams reported that the implementation of office systems was facilitated by the perception that a component could be applied quickly and/or easily. Barriers to implementation included costs, the time required, and lack of agreement with the recommendations. This project demonstrated the feasibility of implementing specific strategies for improving preventive and developmental care for young children in a wide variety of practices. It also confirmed the usefulness of a modified learning collaborative in achieving these results. This model may be useful for disseminating office system improvements to other settings that provide care for young children.


Transcription factors and DNA replication origin selection.
The chromosomes of eukaryotic cells possess many potential DNA replication origins, of which a subset is selected in response to the cellular environment, such as the developmental stage, to act as active replication start sites. The mechanism of origin selection is not yet fully understood. In this review, we summarize recent observations regarding replication origins and initiator proteins in various organisms. These studies suggest that the DNA-binding specificities of the initiator proteins that bind to the replication origins and promote DNA replication are primarily responsible for origin selection. We particularly focus on the importance of transcription factors in the origin selection process. We propose that transcription factors are general regulators of the formation of functional complexes on the chromosome, including the replication initiation complex. We discuss the possible mechanisms by which transcription factors influence the selection of particular origins.


Long Exposure Short Pulse Synchronous Phase Lock Method for Capturing High Dynamic Surface Shape.
In infrared weak target detection systems, high-frequency vibrating mirrors (VMs) are a core component. The dynamic surface shape of the VM has a direct impact on imaging quality and the optical modulation effect, so its measurement is necessary but also very difficult. Measurement of the dynamic surface shape of VMs requires a transiently acquired image series, but traditional methods cannot perform this task, as, when the VM is vibrating at a frequency of 3033 Hz, using high-speed cameras to acquire the images would result in frame rates exceeding 1.34 MFPS, which is currently technically impossible. In this paper, we propose the long exposure short pulse synchronous phase lock (LSPL) method, which can capture the dynamic surface shape using a camera working at 10 FPS. In addition, our proposed approach uses a single laser pulse and can achieve the dynamic surface shape measurement on a single frame image.


Effect of fermentation time and vegetable concentrate addition on quality parameters of organic Botifarra Catalana, a cured-cooked sausage.
The effects of the addition of two different sources of nitrite (pure NaNO2 or a nitrate-rich vegetable concentrate) and three different fermentation times with nitrate-reducing cultures (6, 12, or 24 h at 16 °C) on microbial counts, pH, residual nitrate and nitrite amounts, and susceptibility to oxidation of botifarra catalana sausage were studied. Moreover, curing efficiency, color, tocopherol and tocotrienol contents, oxidative status, and consumer acceptability of these sausages were assessed after vacuum packaging and storage at 4 °C for up to 180 days. Residual nitrate and nitrite amounts were lower than the limits established by the European Union for organic meat products. Longer periods of fermentation produced higher meat curing efficiency ratios, whereas consumer acceptability scores were highest for sausages with added vegetable concentrate. Storage of the sausages caused small quality changes. Therefore, these results indicate that vegetable concentrate is a useful alternative for organic cured-cooked meat products.


Two rare hemoglobin variants in the Çukurova Region of Turkey: Hb E-Saskatoon and Hb G-Coushatta.
Hb E-Saskatoon and Hb G-Coushatta are rare hemoglobin variants that are not a health problem. Herein we present a Turkish woman that was diagnosed as homozygous Hb E-Saskatoon (only the second such case reported from Turkey) and a Turkish boy diagnosed as heterozygote Hb E-Saskatoon. Additionally, 2 Turkish sisters diagnosed as heterozygote Hb G-Coushatta are presented.


Assessment of protein kinase C isozymes by enzyme immunoassay and overexpression of type II in thyroid adenocarcinoma.
A two site enzyme immunoassay which quantitatively identifies types I, II, and III of protein kinase C isozymes has been designed. The soluble protein kinase C isozymes were selectively immobilized by type-specific monoclonal antibodies, MC-1a, -2a, and -3a (H. Hidaka et al., J Biol. Chem., 263: 4523-4526, 1988) which bind to the regulatory domain (NH2-terminal side) of protein kinase C. The amount of each isozyme was then determined using a horseradish peroxidase-conjugated polyclonal antibody raised against the COOH-terminal peptide of protein kinase C. By adding increasing concentrations of the antigen, the range of the assay proved to be 0.51-51, 0.081-8.1, and 0.31-31 nM for types I, II, and III, respectively. This sandwich method was used to determine the level of protein kinase C isozymes in rabbit tissues. Type I was mainly present in the cerebrum and cerebellum; the highest amount of type II isozyme was present in blood platelets [26.0 +/- 3.8 (SE) micrograms/g wet tissue]. We compared the protein kinase C isozyme levels in human normal thyroid gland and thyroid cancer tissues and found that type II protein kinase C specifically increased in thyroid cancer tissues. Immunocytochemical examination using MC-2a revealed that the cytoplasm of the cancer cells showed prominent immunoreactivity for type II isozyme.


Human Motion Intent Description Based on Bumpless Switching Mechanism for Rehabilitation Robot.
This paper aims to improve the performance of an electromyography (EMG) decoder based on a switching mechanism in controlling a rehabilitation robot for assisting human-robot cooperation arm movements. For a complex arm movement, the major difficulty of the EMG decoder modeling is to decode EMG signals with high accuracy in real-time. Our recent study presented a switching mechanism for carving up a complex task into simple subtasks and trained different submodels with low nonlinearity. However, it was observed that a "bump" behavior of decoder output (i.e., the discontinuity) occurred during the switching between two submodels. The bumps might cause unexpected impacts on the affected limb and thus potentially injure patients. To improve this undesired transient behavior on decoder outputs, we attempt to maintain the continuity of the outputs during the switching between multiple submodels. A bumpless switching mechanism is proposed by parameterizing submodels with all shared states and applied in the construction of the EMG decoder. Numerical simulation and real-time experiments demonstrated that the bumpless decoder shows high estimation accuracy in both offline and online EMG decoding. Furthermore, the outputs achieved by the proposed bumpless decoder in both testing and verification phases are significantly smoother than the ones obtained by a multimodel decoder without a bumpless switching mechanism. Therefore, the bumpless switching approach can be used to provide a smooth and accurate motion intent prediction from multi-channel EMG signals. Indeed, the method can actually prevent participants from being exposed to the risk of unpredictable loads.


The dynamics of the schoener-polis-holt model of intra-guild predation.
Intraguild predation occurs when one species (the intraguild predator) predates on and competes with another species (the intraguild prey). A classic model of this interaction was introduced by Gary Polis and Robert Holt building on a model of competing species by Thomas Schoener. A global analysis reveals that this model exhibits generically six dynamics: extinction of one or both species; coexistence about a globally stable equilibrium; contingent exclusion in which the first established species prevents the establishment of the other species; contingent coexistence in which coexistence or displacement of the intraguild prey depend on initial conditions; exclusion of the intraguild prey; and exclusion of the intraguild predator. Implications for biological control and community ecology are discussed.